U96-1494E  Mouse IL-1β ELISA Kit

U96-3112E  Mouse TNF-α ELISA kit

文章摘要：

Recent evidence indicates that the damaged regions in osteoarthritis are accompanied by the accumulation of iron ions. Ferroptosis, as an iron-dependent form of cell death, holds significant implications in osteoarthritis. Melatonin, a natural product with strong scavenging abilities against reactive oxygen species and lipid peroxidation, plays a crucial role in the treatment of osteoarthritis. This study aims to demonstrate the existence of ferroptosis in osteoarthritis and explore the specific mechanism of melatonin in suppressing ferroptosis and alleviating osteoarthritis. Our findings reveal that melatonin reverses inflammation-induced oxidative stress and lipid peroxidation while promoting the expression of extracellular matrix components in chondrocytes, safeguarding the cells. Our research has revealed that NADPH oxidase 4 (NOX4) serves as a crucial molecule in the ferroptosis process of osteoarthritis. Specifically, NOX4 is located on mitochondria in chondrocytes, which can induce disorders in mitochondrial energy metabolism and dysfunction, thereby intensifying oxidative stress and lipid peroxidation. LC-MS analysis further uncovered that GRP78 is a downstream binding protein of NOX4. NOX4 induces ferroptosis by weakening GRP78's protective effect on GPX4 and reducing its expression. Melatonin can inhibit the upregulation of NOX4 on mitochondria and mitigate mitochondrial dysfunction, effectively suppressing ferroptosis and alleviating osteoarthritis. This suggests that melatonin therapy represents a promising new approach for the treatment of osteoarthritis.

最近的证据表明，骨关节炎的损伤区域伴随着铁离子的积累。铁下垂作为一种铁依赖性细胞死亡形式，在骨关节炎中具有重要意义。褪黑素是一种天然产物，具有很强的清除活性氧和脂质过氧化的能力，在骨关节炎的治疗中起着至关重要的作用。本研究旨在证明骨关节炎中铁下垂的存在，并探讨褪黑素抑制铁下垂、缓解骨关节炎的具体机制。我们的研究结果表明，褪黑激素逆转炎症诱导的氧化应激和脂质过氧化，同时促进软骨细胞中细胞外基质成分的表达，保护细胞。我们的研究发现NADPH氧化酶4 (NOX4)在骨关节炎的铁下垂过程中起着至关重要的作用。具体来说，NOX4位于软骨细胞的线粒体上，可诱导线粒体能量代谢紊乱和功能障碍，从而加剧氧化应激和脂质过氧化。LC-MS分析进一步发现GRP78是NOX4的下游结合蛋白。NOX4通过削弱GRP78对GPX4的保护作用并降低其表达而诱导铁下垂。褪黑素可以抑制线粒体NOX4的上调，减轻线粒体功能障碍，有效抑制铁下垂，缓解骨关节炎。这表明褪黑素治疗代表了治疗骨关节炎的一种有希望的新方法。